Steroid[60]fullerene hybrids have been synthesized by Bingel−Hirsch reaction as a contribution to the chemistry of carbon nanoforms. The hybrids were characterized by different spectroscopic NMR experiments and analytical techniques. Theoretical calculations using the DFT-PBE method were performed to predict the most stable conformations for the synthesized compounds and the HOMO-LUMO energy. Some properties such as polarizability, dipole moment, lipophilicity, solvent-accessible surface area, and topological polar surface area, were calculated. Fullerenes and their derivatives have potential antiviral activity due to their specific binding interactions with biological molecules. The ability of fullerene derivatives to interact with the active site of HIV and SARS-Cov-2 proteases was studied by the Autodock Vina program. The C₆₀ cage exhibited an interaction with the phenyl group of PHE residues through π–π and T-shape interactions. Besides, it was observed that the steroid moieties formed H-bonds with the amino acid residues in the active sites of proteins. In addition, van der Waals contacts with the nonpolar protease surface, thereby improving the binding relative to the tested compound. Protein-ligand docking revealed several important molecular fragments that are responsible for the interaction, thus paving the way to study the possible application of these carbon hybrids in medicinal chemistry.

Absorption of solar light and processes of oxidation in living cells lead to biological changes on the cellular level. An overproduction and accumulation of reactive oxygen species (ROS) create an imbalance resulting in oxidative stress, which is responsible for a variety of degenerative diseases. The therapeutic potential of natural antioxidants is a source of inspiration for design of new biologically active compounds. Polyphenolic substances have gained a lot of importance because of their potential as prophylactic and therapeutic agents. Among various naturally occurring polyphenols, hydrolysable tannins represent a large group of strong antiradical and anticancer agents. The biological activities of natural and synthetic gallotannins range from beneficial antioxidants to damaging prooxidants and toxins. Due to their structural diversity and broad array of biological activities have great potential for the development of new pharmaceutically active compounds. Among various naturally occurring gallotannins, penta-1,2,3,4,6-O-galloyl-D-glucose (PGG) was the most widely studied. Presented research has been directed towards the synthesis of new PGG analogues derived from D-glucose, D-mannose, D-ribose and L-rhamnose. The aim of this study was to investigate the biological properties of structurally different gallotannins by various in vitro assays. The evaluation of the antioxidant, free radical scavenging capacity, bioprotective potential and their ability to induce or prevent DNA damage will be discussed in our contribution.

In this work, we investigated the quantitative relationship between biological activity against NSCLC and the molecular structure of a series of 38 cyclohexane-1,3-dione-dimidone derivatives. For this purpose, molecular descriptors calculated by DFT-B3LYP/6-31G, topological and physicochemical analysis were used. The results of the evaluations of the QSAR models developed in this work via MLR and MNLR techniques indicate the high predictive power of these models, for the linear model (R² = 0.913; R²_CV = 0.85, R²_test = 0.934) and (R² = 0.991; R²_CV = 0.82; R²_test = 0.997) for the nonlinear model. Using predictions from the QSAR model, new molecular structures were designed, their activity against NSCLC was evaluated, and the most important interactions between these molecules and the human c-Met protein were predicted. Predictions from QSAR models, molecular docking and evaluation of in silico ADMET properties suggested that 1 of the 16 newly designed molecules is a candidate that may be a drug for NSCLC.

Given the growing number of cancer diseases, new cytostatic drugs are approved daily, often with concomitant development or refinement of some of these drugs aiming at decreasing patient discomfort during administration period (e.g. prodrugs). Classified as highly toxic, they represent a major environmental problem that may potentiate disease occurrences. For newer cytostatics and pro-drugs there are no (or few) reported effects to aquatic organisms, which constraints their prioritization.

In face of the points raised, the IonCytDevice project intended to bridge some of these knowledge gaps and has delivered very important benchmarks. Predictions have been obtained on the environmental impacts of three cytostatics (cyclophosphamide: CYP; 5-fluoroucil: 5-FU; and mycophenolic acid: MPA) and one prodrug (capecitabine: CAP) on freshwater biota, with focus on new species and endpoints likely to be framed in meta-analysis studies as well. The results revealed that, for now, CYP, 5-FU, and CAP (prodrug) pose no risk, whilst MPA was flagged as of high environmental risk.

A number of novel 1, 3, 4-oxadiazole analogues have been designed and synthesized by Condensation of substituted aldehyde/ketone with substituted benzohydrazide to form substituted N'-alkylidene benzohydrazide and then cyclization of N'-alkylidene benzohydrazide to form 1, 3, 4-oxadiazole derivatives. To investigate the antimicrobial data on structural basis, in-silico docking studies of the synthesized compounds (4a-4r) into the crystal structure of E-coli DNA gyrase (Type-2 topoisomerase) using Autodock PyRx virtual screening program were performed to predict the affinity and orientation of the synthesized compounds at the activities by using 6rks PDB. Inhibiting the ATPase activity of gyrase blocks the introduction of negative supercoils in DNA and traps the chromosome in a positively supercoiled state that may have a downstream impact on cell physiology and division. The results indicate that ketone substituted benzohydrazide derivatives show good binding affinity (-8kcal to -9kcal) and electron-withdrawing group such as –NO₂ and -Cl present at R1 increases the affinity of scaffold and DNA gyrase receptors and binds into the specificity pocket. In this pocket, the 1, 3, 4-oxadiazole nucleus of these compounds interacts with the amino acid Alanine A: 421, Valine A: 420, Tyrosine A: 478 and Glutamine A: 381 residues of the target. Also, it is verified by in vitro antimicrobial screening, where all the compounds were active against tested bacterial strains. Among these compounds 4(c), 4(d), (4e), (4h), (4i), 4(m), 4(n), 4(o), 4(p), and (4q) showed good bacterial zone inhibition.

Silver(I) and gold(III) complexes with aromatic nitrogen-containing heterocycles have shown an effective and wide-spectrum antimicrobial activity. The possible mechanism of their antimicrobial activity can be attributed to the interactions of these complexes with biomolecules, including DNA and proteins. In the present study, new silver(I) complex with 1,6-naphthyridine (1,6-naph), {[Ag(1,6-naph)(H₂O)](BF₄)}_n (1) was synthesized and characterized by NMR, IR and UV-Vis spectroscopy, and its crystal structure was determined by single-crystal X-ray diffraction analysis. The complex 1 and the previously reported analogue gold(III) complex [1], [AuCl₃(1,6-naph)], were evaluated for antimicrobial activity against the panel of representative microorganisms, while their cytotoxicity was tested against normal human lung fibroblast cell line (MRC-5). The binding affinity of these complexes with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied to clarify the mode of their antimicrobial activity.

Recently, we synthesized silver(I) complex with the antifungal agent itraconazole, which showed improved anti-Candida potential and therapeutic safety in comparison to itraconazole and rescued the zebrafish embryos of lethal C. albicans infection at safe doses [1]. Inspired by these results, in the present study, three new silver(I) complexes with clinically used azoles, econazole (ecz), clotrimazole (ctz) and voriconazole (vcz), [Ag(ecz)₂]SbF₆ (Ag1), [Ag(ctz)₂]SbF₆ (Ag2) and {[Ag(vcz)₂]SbF₆}_n (Ag3) were synthesized and structurally characterized by elemental microanalysis, mass spectrometry, spectroscopy (¹H NMR, IR and UV-Vis), cyclic voltammetry, molar conductivity measurements and single crystal X-ray diffraction analysis. The spectroscopic and crystallographic results revealed that, in the synthesized silver(I) complexes, azole ligands are monodentately coordinated to the Ag(I) ion through the nitrogen atom forming [Ag(azole)₂]⁺ complex cation. The antimicrobial effect of complexes and azole ligands was evaluated against different Candida species, as well as Gram-positive and Gram-negative bacteria. The synthesized complexes Ag1-3 exhibited good to moderate antimicrobial activity being, in most cases, more active than the corresponding azole ligands. Complexes Ag2 and Ag3 also showed strong inhibitory activity against C. albicans biofilm formation and strong inhibition of C. albicans filamentation at subinhibitory concentrations.

A High performance thin layer chromatographic method for simultaneous estimation of Aliskiren, Amlodipine besylate and Hydrochlorothiazide was developed and validated as per ICH guidelines. Moreover, robustness testing was performed applying a central composite design with k factor having 2 k factorial runs, 2k axial experiments and two center points. High performance thin layer chromatographic separation was performed on aluminium plates precoated with silica gel 60F 254 and acetonitrile: methanol: strong ammonis (10:10:0.1, v/v) as optimized mobile phase. The detection wavelength for simultaneous estimation of three drugs was 250 nm. The Rf values for Aliskiren, Amlodipine besylate and Hydrochlorthiazide were 0.54, 0.32 and 0.78 for, respectively. Percent recoveries in terms of accuracy for the marketed formulation was found to be 101.3-104.4, 100.7-104 and 101.5-103.9 for, Aliskiren, Amlodipine besylate and Hydrochlorthiazide, respectively. The pooled % relative standard deviation values for repeatability studies and intermediate precision studies was found to be less than 2% for Aliskiren, Amlodipine besylate and Hydrochlorthiazide, respectively. All these three factors (methanol content, developing distance and band size) were evaluated in the robustness testing by central composite design and these were found to have an insignificant effect on the retention factor. However, methanol content in total mobile phase as a factor appeared to have significant effect on robustness, compared to band size and developing distance and hence it is important to be carefully controlled. In summary, a novel, simple, accurate and reproducible high performance thin layer chromatographic method was developed, which would be of use in quality control of these tablets.

The four novel complexes [{cis-PtCl(NH₃)(μ-4,4′-bipyridyl)ZnCl(terpy)}](ClO₄)₂ (C1), [{trans-PtCl(NH₃)(μ-4,4′-bipyridyl)ZnCl(terpy)}](ClO₄)₂ (C2), [{cis-PtCl(NH3)(μ-pyrazine)ZnCl(terpy)}](ClO₄)₂ (C3) and [{trans-PtCl(NH₃)(μ-pyrazine)ZnCl(terpy)}](ClO₄)₂ (C4) (where terpy = 2,2′:6′,2′′-terpyridine) were investigated using molecular docking as a powerful in silico method for determination of interaction between hetronuclear complexes and DNA.

The principal interaction between C1 complex and DNA came from H-bonds (at the sites DT19, DA18 nucleotides), and van der Waals forces. Likewise, connection between C2 complex and DNA included covalent H-bonds (DA18, DT19, DG4). On the other hand, complex C3 was bind with DC3, DG2 and DT19 nucleotide basis through conventional H-bonds. The complex C4 was bind with DG10, DT20 and DT19 through conventional H-bonds. Additionally, the complexes C1-C4 show that π interactions were also involved in their binding with DNA. The chelating ability of terpy ligands enhances the complex stability, while their planarity promotes intercalative interaction of the complexes with DNA due to π-stacking between the plane of the aromatic rings and DNA base pairs.

Free radicals are highly reactive and unstable particles that are produced in the body during normal metabolic functions, or by exposure to toxins in the environment such as tobacco smoke and ultraviolet light. Free radicals have a lifespan of only a fraction of a second, but during that time can damage DNA, sometimes resulting in mutations that can lead to various diseases, including heart disease and cancer. The antioxidants can neutralize the unstable particles, reducing the risk of damage. So the design of new substances as a potent antioxidant is an actual problem in the modern world.

For this purpose it were synthesized coordination compounds of Cu(II) and Ni(II) with 1-(morpholin-4-yl)propane-1,2-dione 4-allylthiosemicarbazone (HL). HL was obtained by the condensation reaction between 1-(morpholin-4-yl)propane-1,2-dione and 4-allylthiosemicarbazide in the ethanol solution. Its structure and purity were proved using ¹H and ¹³С NMR spectroscopy. The coordination compounds were synthesized by the interaction of HL with metal salts in a 1:1 and 1:2 molar ratio. The composition of these compounds was determined using elemental analysis: Cu(L)X (X=Cl^-, Br^-, NO₃^-), Ni(HL)₂(NO₃)_2, Ni(L)Cl. These complexes were studied by molar conductivity, IR spectra and X-ray diffraction.

The study of antioxidant activity by the ABTS^•+ method showed that the most active compound is Ni(HL)₂(NO₃)₂. Its IC₅₀ value toward ABTS^•+ is 19.6 µM, so it is 1.7 times more active than trolox, a water-soluble antioxidant which is used in medicine.